The long range goals of this project are to determine the role of I-region associated (Ia) antigens in the regulation of immunocompetent cell interactions and to determine the mechanism of action and site of expression of the major histocompatibility complex (MHC)-linked immune response (Ir) genes. During the past year we have focused our studies on three areas: 1) We have developed the technology to produce cloned lines of I-region restricted, antigen-specific as well as alloreactive guinea pig T cells. We have combined the use of these cloned lines with monoclonal anti-Ia antibodies and demonstrated that individual antigen-specific clones recognize antigen in association with distinct epitopes on Ia molecules. 2) Evidence for the importance of Ia antigens in T cell activation was derived from studies of the syngeneic mixed leukocyte reaction (SMLR) in which we demonstrated that Ia antigens in the absence of foreign antigens activate multiple antigen-specific T cell clones and that the SMLR represents antigen-independent polyclonal activation of antigen-specific T cells mediated through their receptors for self-Ia. 3) We have also developed the immunochemical techniques for the analysis of macrophage antigen processing and have identified a critically important pool of antigen present on the macrophage surface.